Neoplasms contain increased quantities of O-alkyl lipids. In order to detect surface membrane abnormalities in malignant versus non-malignant tumors, we are measuring the O-alkyl lipid content in these membranes by a procedure which isolates these structures as vesicles from a microsomal preparation. O-alkyl lipids of several tumors have now been quantitated by photo densitometry. We have measured O-alkyl and alk-1-enyl lipids of surface membranes of several metastasizing and non-metastasizing tumors. Work now in progress concerns the measurement of a larger series of metastasizing and non-metastasizing tumors. Preliminary results suggest that more malignant tumors may contain greater quantities of O-alkyl phospholipids than less aggressive tumors. We have hypothesized that the mechanism leading to increased O-alkyl lipid synthesis in neoplasms may involve a decrease in long-chain fatty alcohol dehydrogenase activity, thereby providing increased substrate for O-alkyl lipid synthesis. These experiments are still in progress. We have published evidence to show that the O-alkyl lipid bond is formed by the intermediacy of an endiol of acyl-dihydroxyacetone-phosphate. In the absence of fatty alcohol, this mechanism requires the formation of dihydroxyacetone-phosphate which has exchanged the pro-R hydrogen and the release of fatty acid which has retained both carboxyl oxygens. We have previously demonstrated the release of dihydroxyacetone-phosphate which has exchanged the pro-R hydrogen, and we have recently demonstrated that the fatty acid which is released contains both carboxyl oxygens, a mechanism which is different from the usual acyl to oxygen cleavage of an ordinary hydrolysis.